Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

S. Roberts; K. J. Lester; J. L. Hudson; R. M. Rapee; C. Creswell; P. J. Cooper; K. J. Thirlwall; J. R. I. Coleman; G. Breen; C. C. Y. Wong; T. C. Eley

doi:10.1038/tp.2014.83

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

S. Roberts, K. J. Lester, J. L. Hudson, R. M. Rapee, C. Creswell, P. J. Cooper, K. J. Thirlwall, J. R. I. Coleman, G. Breen, C. C. Y. Wong, T. C. Eley^*

^*Corresponding author for this work

Centre for Emotional Health (CEH)

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Abstract

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

Original language	English
Article number	e444
Pages (from-to)	1-5
Number of pages	5
Journal	Translational Psychiatry
Volume	4
DOIs	https://doi.org/10.1038/tp.2014.83
Publication status	Published - 16 Sept 2014

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Copyright 2014 Macmillan Publishers Limited. First published in Translational Psychiatry (2014) 4, e444; doi:10.1038/tp.2014.83. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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title = "Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders",

abstract = "Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.",

author = "S. Roberts and Lester, {K. J.} and Hudson, {J. L.} and Rapee, {R. M.} and C. Creswell and Cooper, {P. J.} and Thirlwall, {K. J.} and Coleman, {J. R. I.} and G. Breen and Wong, {C. C. Y.} and Eley, {T. C.}",

note = "Copyright 2014 Macmillan Publishers Limited. First published in Translational Psychiatry (2014) 4, e444; doi:10.1038/tp.2014.83. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

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AU - Lester, K. J.

AU - Hudson, J. L.

AU - Rapee, R. M.

AU - Creswell, C.

AU - Cooper, P. J.

AU - Thirlwall, K. J.

AU - Coleman, J. R. I.

AU - Breen, G.

AU - Wong, C. C. Y.

AU - Eley, T. C.

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PY - 2014/9/16

Y1 - 2014/9/16

N2 - Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

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Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Abstract

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